Treatment with enfortumab vedotin (EV) plus pembrolizumab achieved a complete response after 3 cycles, and remission was maintained with continued therapy.<h4>Conclusion</h4>This case suggests that EV plus pembrolizumab may be effective for UC-NE and highlights the importance of evaluating nectin-4 and the tumor immune microenvironment when considering treatment strategies for this rare subtype. This evidence concerns the gene NECTIN4 and neoplasm.